Our proposed study on the mechanism and control of DNA Replication will involve biochemical and physical studies on DNA polymerases II and III of E. coli, as well as similar studies on other proteins required for DNA replication. DNA polymerases II and III will be purified on a large scale (5-10 Kg of cells) in order to determine the subunit structure, molecular weight, and binding properties to substrates. The "DNA-binding" proteins of E. coli and phage T7 will be studied with respect to the physical basis of polymerase stimulation and specificity of DNA binding. Mutants of these binding proteins will be sought in an attempt to determine their biological significance. Similar studies (biochemical and physical) will be conducted on the protein products of genes required for DNA replication other than DNA polymerase.